Measles outbreak on a cruise ship in the western Mediterranean, February 2014, preliminary report.

A measles outbreak occurred in February 2014 on a ship cruising the western Mediterranean Sea. Overall 27 cases were reported: 21 crew members, four passengers.For two cases the status crew or passenger was unknown. Genotype B3 was identified. Because of different nationalities of cases and persons on board,the event qualified as a cross-border health threat. The Italian Ministry of Health coordinated rapid response.Alerts were posted through the Early Warning and Response System.

Two cases of chronic lymphoproliferative disorders in psoriatic patients treated with cyclosporine: hairy cell leukemia and Waldenstrom macroglobulinemia.

The real risk of lymphoproliferative disease in psoriatic patients has not yet been defined. Two explanations can be given for the occurrence of these malignancies: the broad immune activation typical of psoriasis and the administration of an immuno-suppressive treatment. A few studies describing the development of non Hodgkin lymphomas in psoriatic patients undergoing cyclosporine A have been published, but data about the occurrence of chronic lymphoproliferative disorders have never been reported. Here we describe the occurrence of hairy cell leukemia and Waldenstrom macroglobulinemia in two psoriatic patients treated with cyclosporine A. It remains unclear in our cases of chronic lymphoproliferative disease, as well as in the reported cases of psoriatic patients who develop lymphomas, whether psoriasis or the immunosuppressive treatment could play a role, although it is not possible to exclude a synergism between these factors.

Cytogenetic and hematological spontaneous remission in a case of acute myelogenous leukemia.

Several cases of spontaneous remission (SR) interrupting the invariably progressive course of untreated acute myeloblastic leukemia (AML) have been reported so far. We shall add to this series the hematological and cytogenetic SR occurring in a 72-yr-old man affected by AML following myelodysplastic syndrome. At diagnosis cytogenetic analysis showed the 48, xy, del (6) (p22-pter), +13, +14 karyotype. Owing to a lobar pneumonia, the chemotherapy was deferred and a broad spectrum antibiotic therapy was established. Supportive care included red cells and platelet transfusions and low-dose corticosteroid. Two months later, after the pneumonia had completely disappeared, a complete remission, lasting about 5 months, was documented on bone marrow morphological and cytogenetical examination, although some degree of myeloid dysplasia persisted. Possible mechanisms of the various SRs described during the course of AML are discussed with a review of the literature.

Temporal change in the use of genotypic resistance testing over the years 1999--2003.

The evaluation of resistance test perception by clinicians over the years 1999--2003 was assessed in an Italian cohort. The results on 2233 samples from 1416 HIV-1 infected patients show an increase in HIV-1 drug resistance test requests over time, with a plateau reached in the last three years. CD4-cell count at the time of genotype request progressively increased. In particular, the median CD4 cell count of drug-treated patients increased from 221x10(6) cells/l [interquartile range (IQR): 109-368] in 1999 to 296x10(6) cells/l (IQR: 166-478) in 2003 (p<0.0001). At the same time, plasma HIV-RNA level progressively decreased from a median of 103,500 copies/ml (IQR: 37,250-260,000) in 1999 to 9,444 copies/ml (IQR: 2,086-41,281) in 2003 (p<0.0001). Overall, data suggest that the genotype test is increasingly considered, and requested also for patients at earlier stages of drug history and/or at less severe disease stage.

Serum transferrin receptor levels in patients with thalassemia intermedia during rHuEPO administration.

In this study we determined the levels of circulating soluble transferrin receptor (sTfR) in six untransfused and two transfused patients affected by beta-thalassemia intermedia during low-dose rHuEPO administration. While the majority of the untransfused patients showed a temporary increment during the first month of treatment, a higher and enduring increase in sTfR concentration was observed in the two transfused patients until rHuEPO was discontinued. The transfused patients showed a significant increase in the reticulocyte index together with the rise in sTfR and an improvement of the anemia, as evidenced by the decrease in their transfusional requirement. These data suggest that basal erythropoietic activity is one of the main causes of differences in responsiveness to low doses of rHuEPO given in thalassemia intermedia.

Serum interleukin-8 levels in thalassemia intermedia.

In this study we determined serum IL-8 levels in 18 untransfused patients with beta-thalassemia intermedia and in 14 subjects affected by HbH disease. As reported in polytransfused homozygous beta-thalassemia, untransfused beta-thalassemia and HbH disease show significantly (p < 0.005) higher serum IL-8 levels than normal controls. Our data suggests that there could be an intrinsic cause for the IL-8 increase in thalassemia intermedia. We think than the hyperactivity of thalassemic macrophages related to chronic hemolysis is the main cause for the increment in cytokines, such as IL-8, found in thalassemic syndromes.

Interferon-alpha 2a therapy in CML: disappearance of BCR/ABL transcript in a case of long-lasting continuous cytogenetic conversion.

Seventy months after diagnosis, minimal residual disease is undetectable in a patient with Philadelphia chromosome-positive chronic myelogenous leukemia (CML) in long-lasting continuous cytogenetic conversion (CCC), achieved through alpha 2a-interferon (IFN-alpha) therapy. Fluctuating molecular remission, evaluated with the two-stage reverse transcriptase-polymerase chain reaction (RT-PCR) with nested primers, has persisted for two years at the maximum tolerable dose of IFN alpha (1.5 x 10(6) IU per day).

A 12-year preventive program for beta-thalassemia in Northern Sardinia.

From 1980 to 1991, 6.3% of the adult population of the province of Sassari, Northern Sardinia, underwent voluntary beta-thalassemia screening. Of the 28,000 subjects examined, 15.7% proved to be heterozygotes for beta-thalassemia. In addition, the screening of 7500 students in 26 villages in Sassari province fixed the frequency of beta-thalassemia in this part of Sardinia at 10.4%. Of the 539 couples at risk to be expected from this figure, the screening detected 43% (234). The data suggest that inductive screening played a major role in the efficiency of this preventive beta-thalassemia program. Follow up of 221 pregnancies found to be at risk for homozygous beta-thalassemia and referred to the Antenatal Diagnosis Service, Cagliari, Southern Sardinia, showed that antenatal diagnosis was carried out in 80% of them. The overall percentage of couples refusing antenatal diagnosis was 10.8%, but over the years the acceptance rate for the procedure increased from 87% to 96%. Atypical hematological findings in 1.5% of 468 members of the couples at risk required globin chain synthesis and molecular analyses to define the precise beta-thalassemia genotype. Heterogeneous "mild" beta-thalassemia mutations as well as coexisting delta-thalassemia were found in silent type I and type II beta-thalassemia carriers which, without chain synthesis and DNA investigations, would have escaped detection.

Serum erythropoietin levels in thalassemia intermedia.

Serum concentrations of erythropoietin (EPO) were determined by immunoassay in 45 patients with thalassemia intermedia (TI). The mean serum level of EPO was significantly higher in the thalassemic patients than in the controls, but transfused subjects had lower pretransfusional serum concentrations of EPO than untransfused ones. An inverse relationship between the serum values of EPO and total hemoglobin was observed only in the untransfused thalassemic patients. These data suggest that in TI, even a low transfusional regimen may cause a decrease in serum concentration of EPO, independent of the level of total Hb.

Incidence and clinical study of ectopic erythropoiesis in adult patients with thalassemia intermedia.

We carried out total body computerized tomography (CT) studies and examined the retrospective clinical data of 29 adult patients with thalassemia intermedia (TI) to evaluate the incidence, features and pathogenesis of ectopic erythropoiesis (EE), located chiefly at the paravertebral gutters in the thorax, was present in 65.5% of the patients; 15% of them had severe clinical complications. We found a clear relationship between EE development and early presentation age of thalassemia, splenectomy and the presence of 100% fetal hemoglobin. The frequent occurrence of EE suggests that CT screening of patients with thalassemia intermedia should be mandatory. We also recommend radiotherapy as a preventive measure for the clinical complications of thalassemic patients with EE.

[Current views of thalassemia intermedia]. / Vedute attuali sulla talassemia intermedia.

Recently the molecular bases of thalassemia intermedia have been elucidated in several populations. In general this attenuated, non-transfusion dependent form of homozygous beta-thalassemia is mainly determined by a) the co-inheritance of deletion alpha-thalassemia; b) the presence of the so-called mild beta-thalassemia mutations; and more rarely, c) the inheritance of genetic conditions able to enhance the gamma-globin chain expression in adult life. Although there are several complex genetic and acquired interactions involved in the wide clinical heterogeneity of thalassemia intermedia, data in Italians indicate a definite genotype-phenotype relationship in conditions such as the co-inheritance of at least two alpha-thalassemia genes in severe and mild homozygous beta-thalassemia; the molecular homozygosity or double heterozygosity for the -87, -101 and IVS1(nt6) beta(+)-thalassemia mutations; and the coexistence of structural gamma-globin gene defects, i.e. Sicilian and Sardinian delta beta-thalassemias, deletional and non-deletional hereditary persistence of fetal hemoglobin and the polymorphism for the -158 XmnI G gamma restriction site. Thalassemia intermedia resulting from the inheritance in heterozygous beta-thalassemia of triple alpha-globin gene complex or the presence of dominant beta-thalassemia is also described and the role of these new informations in genetic counselling is discussed.

[Differential diagnosis of thalassemia syndromes]. / Diagnosi differenziale delle sindromi talassemiche.

In Sardinia, as in other areas with a high incidence of thalassemia syndromes, a prevention program based on the detection of healthy carriers through mass screening and on prenatal diagnosis in the at-risk couples has been in course for several years. The commonly adopted beta-thalassemia flow-chart consists of a first operative step involving simple and widely standardized tests: the estimation of red cell indices, the measurement of Hb A2 and Hb electrophoresis. These investigations permit the identification of the majority of the at-risk couples for beta-thalassemia. However, the not infrequent evidence of Hb A2 borderline levels, with or without microcytosis, isolated microcytosis or Hb F increased values, causes some problems in differential diagnosis, because these findings can indicate the presence of silent beta-thalassemic traits or other beta-thalassemic like states. A diagnostic definition of these unusual hematological phenotypes is particularly important for the identification of eventual at-risk couples. In this paper we report our data concerning the voluntary screening for beta-thalassemia carried out in North Sardinia. The operative flow-chart is shown. In a population with a high incidence of phenotypically heterogeneous thalassemic syndromes, such as that of Sardinia, differential diagnosis of thalassemic traits can require molecular studies. This molecular characterization, which could be carried out in specialized reference centers, is today absolutely necessary both for exact identification of at-risk couples and eventual prenatal diagnosis.

[Purification and properties of cytoplasmic and mitochondrial hexokinase from the rabbit brain]. / Purificazione e proprieta' dell'esocinasi citoplasmatica e di quella mitocondriale da cervello di coniglio.

The soluble Hexokinase from rabbit brain was purified 4,700-fold to near homogeneity by a combination of ion-exchange chromatography, dye-ligand chromatography and affinity chromatography. The purified enzyme showed a specific activity of 110 units/mg of protein and was obtained in 70% yield. The properties of the purified cytoplasmic hexokinase were compared with those of the solubilized mitochondrial enzyme. No significant differences were found in M.W., pI and electrophoretic mobility. However, the temperature dependence of activity and specificity for several hexose substrates were markedly different.